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A Study of AB-218 in Patients With IDH1 Mutated Low Grade Glioma

EARLY_PHASE1RECRUITING

The aim of this clinical trial is to evaluate the feasibility of undertaking a Phase 0 surgical study in patients with diagnosis of a IDH1 mutated Low Grade Glioma (LGG) who have not received prior radiation or chemotherapy and are planned to undergo surgical resection.

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Study details:

This is a single arm, open label Phase 0 trial to assess the feasibility, pharmacokinetics and pharmacodynamics of treatment with AB-218 following biopsy and prior to resection in patients with IDH1 mutated glioma. Participants will receive treatment in 2 parts:. Part A: Biopsy followed by 1 cycle (28 days) of Safusidenib Erbumine (formerly AB-218), an orally available, small molecular inhibitor of mutated IDH1, then safe maximal resection of the tumour.

Part B: Following recovery from surgery, patients will receive at least 12 cycles of Safusidenib, subject to ongoing documented evidence of clinical benefit, until disease progression or unacceptable toxicity. It is expected that 10 patients will take part in this study. It is anticipated this research study will enable investigators to objectively measure the biological activity of Safusidenib in patients with IDH1 mutated LGG.

Anti-tumour activity will be assessed by RANO response criteria. The investigators have previous experience in pre-treating patients with GBM prior to surgery with systemic therapies and collecting tumour, peri-tumour and normal brain tissues for PK, PD and biomarker evaluation.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

Histologically confirmed LGG or new diagnosis of LGG based on MRI

Tumours suitable for biopsy and safe for maximal resection in the opinion of the treating neurosurgeon

Patients who in the consensus of the treating neurosurgeon require resection of the brain tumour.

Patients who do not require immediate definitive resection of the brain tumour in the opinion of the treating neurosurgeon

Measurable and/or evaluable disease as per LGG-RANO criteria

Age ≥ 18 years of age.

ECOG performance score 0-1

Life expectancy of at least 24 months, in the opinion of the investigator

Adequate haematological, renal and hepatic function

Reproductive and contraception criteria as prescribed

Exclusion criteria

Patients who require immediate definitive resection due to degree of mass effect or symptoms

Multicentric / multifocal tumour

Tumour involves cerebellum or brainstem

Patients who have undergone surgery for glioma within 24 months of study enrolment

Patients who have received prior chemotherapy and / or radiation for a diagnosis of glioma

Patients with contraindications to MRI or unwilling to undergo MRI

History of central nervous system bleeding as defined by stroke within 6 months before enrolment

Evidence of acute intracranial / intra-tumoural haemorrhage, except for participants with stable grade 1 haemorrhage

Other general criteria including: i) ECG abnormalities ii) significant comorbidity or infection iii) Prior malignancy iv) Recent surgery v) Known allergy or sensitivity to any of the excipients in the investigational product vi) no contraindicated concomitant medications

History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator would pose a risk to participant safety or interfere with the study evaluation, procedures or completion

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Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2022-10-11

Primary completion: 2024-12-01

Study completion finish: 2025-12-01

Study type

TREATMENT

Phase

EARLY_PHASE1

Trial ID

NCT05577416

Intervention or treatment

PROCEDURE: Biopsy

DRUG: Part A: Safusidenib Erbumine

PROCEDURE: Surgery (maximal resection)

DRUG: Part B: Safusidenib Erbumine

Conditions

• Glioma

Condition: Glioma
PROCEDURE: Biopsy and other drugs
Melbourne, Victoria, Australia
Sponsor: Melbourne Health

You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

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Find a site

Closest Location:

Royal Melbourne Hospital

Research sites nearby

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Royal Melbourne Hospital
Melbourne, Victoria, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Safusidenib Erbumine (AB-218) Part A: Peri-operative treatment (Phase 0); Part B: Post operative adjuvant therapy (phase 2)	PROCEDURE: Biopsy Patients will undergo stereotactic biopsy by craniotomy or burr hole.

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
Phase 0: Feasibility of Phase 0 study in patient population	Number of patients to complete all planned investigations and procedures	14 months
Phase 0: pharmacokinetic analysis of tumour tissue	Total and unbound AB-218 in tumour tissue	4 weeks
Phase 0: pharmacokinetic analysis of cerebrospinal fluid (CSF)	Total and unbound AB-218 in CSF	4 weeks
Phase 2: Number of Adverse events	Number of adverse events (AEs) according to NCI CTCAE v 5	up to 30 days after last study dose
Phase 2: Incidence of drug related adverse events	Drug related adverse events	up to 30 days after last study dose
Phase 2: Incidence of dose limiting toxicity	Dose limiting toxicity events	up to 30 days after last study dose

Secondary outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
Phase 0: Incidence of treatment emergent Adverse events	Treatment emergent adverse events (AEs) according to NCI CTCAE v 5	during 1 cycle of AB-128, prior to maximal resection (4 weeks)
Phase 0: Safety of planned craniotomy and resection after stereotactic biopsy and treatment with AB-218	30-day morbidity and mortality post surgery	30 days after maximal resection
Phase 0: Pharmacodynamic (PD) analysis of AB-218 in tumour	Changes in 2-hydroxyglutarate (2-HG) levels in tumour	after maximal resection (4 weeks), at progression (optional)
Phase 0: Pharmacodynamic (PD) analysis of AB-218 in cerebrospinal fluid (CSF)	Changes in 2-hydroxyglutarate (2-HG) levels in cerebrospinal fluid (CSF)	after maximal resection (4 weeks), at progression (optional)
Phase 0: Pharmacodynamic (PD) analysis of AB-218 in plasma	Changes in 2-hydroxyglutarate (2-HG) levels in plasma	after maximal resection (4 weeks), monthly during treatment, at progression (optional)
Phase 0: anti-tumour activity	Objective response (LGG RANO assessment)	4 weeks
Phase 0: Identify factors that can improve the patient experience quality of the service provided to participants using Research Participant Perception Survey short form (RPPS)	Understanding the patients' perspective on the peri-operative design and satisfaction with study procedures	4 months post op
Phase 2: Identify factors that can improve the patient experience quality of the service provided to participants using Research Participant Perception Survey short form (RPPS)	Understanding the patients' perspective on the peri-operative design and satisfaction with study procedures	4 months post op
Phase 2: anti-tumour activity	Objective response (LGG RANO assessment)	12 weekly until progression

Frequently Asked Questions

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References

Clinical Trials Gov: A Study of AB-218 in Patients With IDH1 Mutated Low Grade Glioma